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Du Fu,Qi Xin,Zhang Aotong,Sui Fanfan,Wang Xuemin,Proud Christopher G.,Lin Cunzhi,Fan Xinglong,Li Jing 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
PD-L1 is abnormally regulated in many cancers and is critical for immune escape. Fully understanding the regulation of PD-L1 expression is vital for improving the clinical efficacy of relevant anticancer agents. TGF-β plays an important role in the low reactivity of PD-1/PD-L1 antibody immunotherapy. However, it is not very clear whether and how TGF-β affects PD-L1 expression. In the present study, we show that TGF-β upregulates the expression of the transcriptional coactivator MRTF-A in non-small-cell lung cancer cells, which subsequently interacts with NF-κB/p65 rather than SRF to facilitate the binding of NF-κB/p65 to the PDL1 promoter, thereby activating the transcription and expression of PD-L1. This leads to the immune escape of NSCLC cells. This process is dependent on the activation of the TGF-β signaling pathway. In vivo, inhibition of MRTF-A effectively suppresses the growth of lung tumor s y ngrafts with enrichment of NK and T cells in tumor tissue. Our study defines a new signaling pathway that regulates the transcription and expression of PD-L1 upon TGF-β treatment, which may have a significant impact on research into the application of immunotherapy in treating lung cancer.
Fu Xin,Jie Zhang,Zhiyuan Chen,Xiaorong Du 기술경영경제학회 2016 ASIAN JOURNAL OF TECHNOLOGY INNOVATION Vol.24 No.3
This paper aims to fill the gap in the extensive literature on the results of interaction betweenpublic and private R&D expenditures. Two types of public R&D subsidies, the appropriationsand loan interest, are investigated in the effect of public subsidies by applying for a uniquemicro data set of Chinese manufacturing firms combined with the Innovation Fund forSmall and Medium Technology-based Firms (Innofund). The results are consistent with theprediction that loan interest subsidies based on more competitive selective system are moreeffective for the public R&D subsidies than the appropriations. Firms’ heterogeneity,measured by state-owned enterprises (SOEs) and private-owned enterprises (POEs), is testedfor the different impact of public subsidies on corporate R&D investment. The results showthat the crowding-in effect is mainly driven by POEs, not by SOEs, which confirms thetheoretical assumption by Aghion and Tirole that the agency problem play a dominant rolein corporate R&D activities. An improved econometric method, combined propensity scorematching with difference-in-differences estimation strategy, is applied for correcting theselection bias. Our results are robust to different matching techniques.
Engineering Bifunctional Antibodies with Constant Region Fusion Architectures
Du, Juanjuan,Cao, Yu,Liu, Yan,Wang, Ying,Zhang, Yong,Fu, Guangsen,Zhang, Yuhan,Lu, Lucy,Luo, Xiaozhou,Kim, Chan Hyuk,Schultz, Peter G.,Wang, Feng American Chemical Society 2017 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.139 No.51
<P>We report a method to generate bifunctional antibodies by grafting full-length proteins into constant region loops of a full-length antibody or an antigen-binding fragment (Fab). The fusion proteins retain the antigen binding activity of the parent antibody but have an additional activity associated with the protein insert. The engineered antibodies have excellent <I>in vitro</I> activity, physiochemical properties, and stability. Among these, a Her2 × CD3 bispecific antibody (BsAb) was constructed by inserting an anti-Her2 single-chain variable fragment (ScFv) into an anti-CD3 Fab. This bispecific antibody efficiently induces targeted cell lysis in the presence of effector cells at as low as sub-picomolar concentrations <I>in vitro</I>. Moreover, the Her2 × CD3 BsAb shows potent <I>in vivo</I> antitumor activity in mouse Her2<SUP>2+</SUP> and Her2<SUP>1+</SUP> xenograft models. These results demonstrate that insertion of a full-length protein into non-CDR loops of antibodies provides a feasible approach to generate multifunctional antibodies for therapeutic applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2017/jacsat.2017.139.issue-51/jacs.7b09641/production/images/medium/ja-2017-09641x_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja7b09641'>ACS Electronic Supporting Info</A></P>
Du, Xiao Fei,Jiang, Cheng Zhe,Wu, Chun Fu,Won, Eun-Kyung,Choung, Se-Young 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9
We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.
Some Motifs Were Important for Myostatin Transcriptional Regulation in Sheep (Ovis aries)
Du, Rong,An, Xiao-Rong,Chen, Yong-Fu,Qin, Jian Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.4
Many motifs along the 1.2 kb myostatin promoter (MSTNpro) in sheep have been found by the MatInspecter program in our recent study. To further verify the role of the motifs and better understand the transcriptional regulation mechanism of the myostatin gene in sheep, the reporter gene EGFP (enhanced green fluorescent protein) was selected and the wild-type (W) vector MSTNPro$^W$-EGFP or motif-mutational (M) vector MSTNPro$^M$-EGFP were constructed. The transcriptional regulation activities were analyzed by detecting the fluorescence strength of EGFP in C2C12 myoblasts transfected with the vectors. The results showed that E-box (E) 3, E4, E5 and E7, particularly E3, E5 and E7, had important effects on the activity of the 1.2 kb sheep myostatin promoter. In addition, we also detected several other important motifs such as MTBF (muscle-specific Mt binding factor), MEF2 (myocyte enhancer factor 2), GRE (glucocorticoid response elements) and PRE (progesterone response elements) along the sheep myostatin promoter by the mutational analysis.
Fu Xiaoying,Guo Huimin,Cong Wei,Du Hongwei,Meng Xiang-Cai 경희대학교 융합한의과학연구소 2017 Oriental Pharmacy and Experimental Medicine Vol.17 No.4
Approximately 1200 years ago, the close association between the quality of medicine and the producing area was well known in China. Recent work has shown conclusively that the quality of herbal medicine is influenced by unfavorable conditions, but the exact cause remains unclear and is a difficult problem in research on herb resources. Fresh roots of S. baicalensis were exposed to temperatures of 35 °C ~ 55 °C, and the H2O2 level remained relatively inflexible. The superoxide dismutase (SOD) and catalase (CAT) activities remained stable at 35 °C and 45 °C but decreased on day 1 at 55 °C. The excess ROS due to the high temperatures must be removed by another pathway. Our study reported that the phenylalanine ammonia-lyase (PAL) activities rose. The fresh roots were exposed to 55 °C for 2 days, the baicalin increased by 38.5%, the wogonoside by 24.1%, and the baicalein by 37.0%. This method can substantially improve the quality of Radix Scutellariae.
Effects of Trichostatin A on Cumulus Expansion during Mouse Oocyte Maturation
Du, Ming,Fu, Xiangwei,Zhou, Yanhua,Zhu, Shien Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.11
This study was conducted to investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05). To determine the underlying mechanism, the expression levels of several key factors that play crucial roles in cumulus expansion including components of extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth differentiation factor 9 (GDF9) were measured in control and TSA treated samples by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by Western blotting. The expression levels of the ECM genes were significantly decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no significant effect on GDF9 protein expression (p>0.05). Collectively, these results suggested that TSA treatment altered ECM gene expression and blocked ERK1/2 activation to inhibit cumulus expansion in the mouse.
Du, J.,Bao, J.,Fu, X.,Lu, C.,Kim, S.H. Elsevier 2016 Applied Catalysis B Vol.184 No.-
<P>A mesoporous sulfur-modified iron oxide (MS-Fe) was prepared as a heterogeneous H2O2 catalyst for degradation of BPA. The physico-chemical properties of MS-Fe and bare M-Fe were characterized by BET surface area measurement, SEM, XRD, MIR and XPS. Both M-Fe and MS-Fe composites appeared as cubic microparticles with abundant pores and cracks as well as large surface area. As depicted by XRD, EDX and XPS, M-Fe is mainly consisted of hematite while MS-Fe is a kind of S-doped iron oxide with about 5-6% of sulfur element in terms of atomic ratio. In contrast to the poor catalytic activity of bare M-Fe, the MS Fe composites showed greatly improved efficiencies for H2O2 activation for BPA degradation. The high catalytic activity of this new Fenton-like catalyst can be obtained at different initial pH in range of 3.0-9.0. The time evolution of degradation of BPA followed pseudo-first-order kinetics, and the first-order rate constants showed a linear relationship with parameters of initial pH, catalyst dosage and concentration of BPA. However, the H2O2 dosage showed a dual effect on BPA degradation because excessive H2O2 addition lead to scavenging of hydroxyl radicals ((OH)-O-center dot). The investigation of working mechanisms of MS Fe suggested a synergistic effect of homogeneous and heterogeneous degradation reaction, wherein a strong acidic environment, abundant surface-bonded hydroxyl group and electron-mediating effect of sulfur all contributed to fast activation of H2O2. Overall, this new material overcomes the limitation of narrow working pH range and shows a fast oxidation of BPA with a low H2O2 and catalyst dosage, would have a good potential for environmental application. (C) 2015 Elsevier B.V. All rights reserved.</P>